ABSTRACT
Objective To investigate the effects of memantine hydrochloride on the learning and memory function in vascular dementia (VaD) in rats and its possible mechanism.Methods A rat VaD model was induced by using permanent bilateral common carotid artery ligatioa A total of 36 SD rats were randomly divided into sham-operation group, VaD group,and memantine group (memantine hydrochloride was given by intragastric administration, once a day, for eight weeks) (n = 12 in each group). Y maze test was used to observe their behavioral changes. Immunohistochemistry technique was used to detect the changes of the expressions of cAMP responsive element binding protein (CREB) and cytochrome c (CytC) in hippocampal CA1 region and cortex; and TUNEL method was used to detect neuronal apoptosis. Results The learning and memory abilities in memantine group were 50.17 ± 5.56 and 7.08 ± 0.90 respectively, and they were significantly better than 66.36 ± 5.41 and 4.64 ± 1.03 in the VaD group (all P＜0.01); the mean absorbencies of CREB in hippocampal CA1 region and cortex were 147.51 ± 7.11 and 155.37 ± 4.52, respectively, and they were significantly higher than 135.11 ± 8.52 and 142.39 ± 5.24 in the VaD group (all P＜0.01); and the mean absorbencies of CytC in hippocampal CA1 region and cortex were 116.53 ± 4.91 and 113.51 ± 6.05, and they wre significantly lower than 136.65 ±7.43 and 138.09 ±4.88 in the VaD group (all P ＜ 0.01); the extent of apoptosis in the memantine group was also improved significantly compared to the VaD group. Conclusions Memantine hydrochloride may improve the learning and memory function in VaD rats by upregulating the expression of CREB and inhibiting the release of CytC and neuronal apoptosis.
